The role of TDRG1 in tumorigenesis and the progression of seminoma, as well as its role in regulating chemosensitivity of seminoma to cisplatin through the PI3K/Akt/mTOR signaling pathway, has been previously defined. However, the detailed mechanism underlying TDRG1 expression and concomitant chemoresistance conditions are unknown. Furthermore, it has been reported that non‐protein‐coding RNAs play an important role in a variety of vital processes including cellular chemosensitivity. However, the role of non‐protein‐coding RNAs in regulating the chemosensitivity of seminoma remains unknown. In this study, using microarray analysis, we found that long non‐coding RNA H19 was upregulated while miRNA‐106b‐5p was downregulated in an established cisplatin‐resistant TCam‐2 cell line. Moreover, H19 acts as a miRNA‐106b‐5p sponge and thus impairs the function of miRNA‐106b‐5p on its target gene, TDRG1. Based on these findings, we propose that H19 promotes the expression of TDRG1 by sequestering miRNA‐106b‐5p and uses this mechanism to facilitate cell survival in cisplatin‐based chemotherapeutic conditions. These findings elucidate the mechanisms, at least partially, applied to deregulate TDRG1 and cisplatin sensitivity, and may provide new therapeutic possibilities for chemoresistant seminoma.

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We previously identified testis developmental related gene 1 (TDRG1), a gene implicated in proliferation of TCam‐2 seminoma cells. Recent evidence has revealed that autophagy influences the chemosensitivity of cancer cells to chemotherapy. However, whether TDRG1 protein regulates autophagy in seminoma cells and influences their sensitivity to cis‐dichlorodiammine platinum (CDDP) remains unknown. In this study, we used TCam‐2 cells and male athymic BALB/c nude mice with xenografts of TCam‐2 cells to investigate autophagy, cell viability, apoptosis and the p110β/Rab5/Vps34 (PI3‐kinase Class III) pathway under the conditions of TDRG1 overexpression or knockdown and with or without CDDP treatment. We found that TDRG1 upregulation promoted autophagy in both TCam‐2 cells and seminoma xenografts via p110β/Rab5/Vps34 activation. Inhibition of autophagy reduced cell viability and promoted apoptosis during CDDP treatment of TCam‐2 cells. Similarly, TDRG1 knockdown inhibited autophagy, reduced cell viability and promoted apoptosis during CDDP treatment of TCam‐2 cells. TDRG1 knockdown inhibited tumour growth and promoted apoptosis in TCam‐2 cell xenografts, whereas TDRG1 overexpression had the opposite effect. According to these results, we propose that high expression of TDRG1 promotes autophagy through the p110β/Rab5/Vps34 pathway in TCam‐2 cells. TDRG1 overexpression promotes autophagy and leads to CDDP resistance, whereas TDRG1 knockdown inhibits autophagy and promotes chemosensitivity to CDDP both in vivo and in vitro. This study has uncovered a novel role of TDRG1 in reducing chemoresistance during CDDP treatment and provides potential therapeutic strategies for the treatment of human seminoma.

Aim To investigate the possibility and mechanism of microenergy acoustic pulses (MAP) for activating tissue resident stem/progenitor cells within pelvic and urethral muscle and possible mechanism. Methods The female Zucker Lean and Zucker Fatty rats were randomly divided into four groups: ZL control, ZLMAP, ZF control, and ZFMAP. MAP was applied at 0.033 mJ/mm2, 3 Hz for 500 pulses, and the urethra and pelvic floor muscles of each rat was then harvested for cell isolation and flow cytometry assay. Freshly isolated cells were analyzed by flow cytometry for Pax‐7, Int‐7α, H3P, and EdU expression. Meanwhile, pelvic floor muscle‐derived stem cells (MDSCs) were harvested through magnetic‐activated cell sorting, MAP was then applied to MDSCs to assess the mechanism of stem cell activation. Results Obesity reduced EdU‐label‐retaining cells and satellite cells in both pelvic floor muscle and urethra, while MAP activated those cells and enhanced cell proliferation, which promoted regeneration of striated muscle cells of the pelvic floor and urethral sphincter. Activation of focal adhesion kinase (FAK)/AMP‐activated protein kinase (AMPK) /Wnt/β‐catenin signaling pathways by MAP is the potential mechanism. Conclusions MAP treatment activated tissue resident stem cells within pelvic floor and urethral muscle in situ via activating FAK‐AMPK and Wnt/β‐catenin signaling pathway.

Background Neurogenic erectile dysfunction (ED) is often refractory to treatment because of insufficient functional nerve recovery after injury or insult. Noninvasive mechano-biological intervention, such as microenergy acoustic pulse (MAP), low-intensity pulsed ultrasound, and low-intensity extracorporeal shockwave treatment, is an optimal approach to stimulate nerve regeneration. Aim To establish a new model in vitro to simulate nerve injury in neurogenic ED and to explore the mechanisms of MAP in vitro. Methods Sprague-Dawley rats were used to isolate Schwann cells (SCs), major pelvic ganglion (MPG), and cavernous nerve with MPG (CN/MPG). SCs were then treated with MAP (0.033 mJ/mm2, 1 Hz, 100 pulses), and SC exosomes were isolated. The MPG and CN/MPG were treated with MAP (0.033 mJ/mm2, 1 Hz) at different dosages (25, 50, 100, 200, or 300 pulses) or exosomes derived from MAP-treated SCs in vitro. Outcomes Neurite growth from the MPG fragments and CN was photographed and measured. Expression of neurotropic factors (brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3) was checked. Results Neurite outgrowth from MPG and CN/MPG was enhanced by MAP in a dosage response manner, peaking at 100 pulses. MAP promoted SC proliferation, neurotropic factor (brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3) expression, and exosome secretion. SC-derived exosomes significantly enhanced neurite outgrowth from MPG in vitro. Clinical Implications MAP may have utility in the treatment of neurogenic ED by SC-derived exosomes. Strength & Limitations We confirmed that MAP enhances penile nerve regeneration through exsomes. Limitations of this study include that our study did not explore the exact mechanisms of how MAP increases SC exosome secretion nor whether MAP modulates the content of exosomes. Conclusion This study revealed that neurite outgrowth from MPG was enhanced by MAP and by SC-derived exosomes which were isolated after MAP treatment. Our findings indicate that one mechanism by which MAP induces nerve regeneration is by stimulation of SCs to secrete exosomes.

Peripheral nerve damage, such as that found after surgery or trauma, is a substantial clinical challenge. Much research continues in attempts to improve outcomes after peripheral nerve damage and to promote nerve repair after injury. In recent years, low-intensity pulsed ultrasound (LIPUS) has been studied as a potential method of stimulating peripheral nerve regeneration. In this review, the physiology of peripheral nerve regeneration is reviewed, and the experiments employing LIPUS to improve peripheral nerve regeneration are discussed. Application of LIPUS following nerve surgery may promote nerve regeneration and improve functional outcomes through a variety of proposed mechanisms. These include an increase of neurotrophic factors, Schwann cell (SC) activation, cellular signaling activations, and induction of mitosis. We searched PubMed for articles related to these topics in both in vitro and in vivo animal research models. We found numerous studies, suggesting that LIPUS following nerve surgery promotes nerve regeneration and improves functional outcomes. Based on these findings, LIPUS could be a novel and valuable treatment for nerve injury-induced erectile dysfunction.

Aim Obesity is a strong independent risk factor for urinary incontinence. Effective therapeutic approaches for obesity‐associated stress urinary incontinence (OA‐SUI) are lacking as the mechanisms remain unclear. The aim of our study is to explore the impacts of microenergy acoustic pulse (MAP) therapy on urethral and pelvic floor muscle structure and function in female lean and fatty rats. Methods A total 24 Zucker fatty (ZF) and 24 Zucker lean (ZL) female 24‐week‐old rats were grouped into four groups: ZL control, ZLMAP, ZF control, and ZFMAP. For MAP treatment, 500 pulses were delivered at an energy level of 0.033 mJ/mm 2 and a frequency of 3 Hz and were applied twice a week for 4 weeks. After a 1‐week washout, all rats underwent conscious cystometry and leak‐point pressure (LPP) measurements followed by ex vivo organ‐bath assay and histological study. Results ZF rats had lower LPP as compared to ZL rats, and MAP treatment significantly improved LPP in ZF rats (P < .05). Impaired muscle contractile activity (MCA) in organ‐bath study was noted in ZF rats. MAP treatment significantly increased MCA in ZF rats (P < .05) and also increased the thickness of the striated muscle layer and the number of neuromuscular junctions (NMJs). In situ, MAP activated muscle satellite cells significantly (P < .05). Conclusions Obesity impairs the function of both the urethral sphincter and the pelvic floor and leads to atrophy and distortion of the striated muscle in obese female rats. These issues contribute to OA‐SUI. MAP improves continence by stimulating muscle regeneration and nerve innervation as well as by activating satellite cells.

Background: Stress urinary incontinence (SUI) is a common disorder with high prevalence in women across their life span, but there are no non-surgical curative options for the condition. Stem cell-based therapy, especially endogenous stem cell therapy may be a potential treatment method for SUI. The aims of this study are to identify, isolate, and assay the function of urethral striated muscle derived stem/progenitor cells (uMDSCs) and to assess uMDSC response to microenergy acoustic pulses (MAP).Methods: Urethral striated muscle was identified utilizing 3D imaging of solvent organs (3DISCO) and immunofluorescence (IF). uMDSCs were isolated and purified from Zucker Lean (ZL) (ZUC-LEAN) (ZUC-Leprfa 186) rats, with magnetic-activated cell sorting (MACS) and pre-plating methods. The stemness and differentiation potential of the uMDSCs were measured by cell proliferation, EdU, flow cytometry, IF, and Western blot.Results: Comparison of the cell proliferation assays between MACS and pre-plating reveals the advantage of MACS over pre-plating. In addition, the study reveals that uMDSCs form myotubes when treated with MAP. Conclusions:The uMDSCs within female rat urethral striated muscle could be a therapeutic target of MAP in managing SUI.